Facilitators of and barriers to gastric cancer and precursor diagnosis among South Texas residents: Social determinants of health

Abstract Background Latinos/Hispanics are at higher risk for developing gastric cancer (GC) compared with non‐Hispanic whites, and social determinants of health (SDoH) are thought to contribute. Aims/Materials and Methods This study addressed SDoH and their interactions contributing to disparities in the testing and treatment of Helicobacter pylori (HP) infection and diagnosis of GC and its known precursors, among Latinos/Hispanics relative to non‐Latinos at two affiliated but independent health systems in San Antonio, Texas, using a mixed methods approach. Results Secondary data abstraction and analysis showed that GCs represented 2.6% (n = 600) of our population. Men and older individuals were at higher GC risk. Individuals with military insurance were 2.7 times as likely to be diagnosed as private insurance. Latinos/Hispanics had significantly (24%) higher GC risk than Whites. Poverty and lack of insurance contributed to GC risk among the minorities classified as other (Asians, Native Americans, Multiracial; all p < 0.01). All SDoH were associated with H. pylori infection (p < 0.001). Qualitative analysis of patient and provider interviews showed providers reporting insurance as a major care barrier; patients reported appointment delays, and lack of clinic staff. Providers universally agreed treatment of H. pylori was necessary, but disagreed on its prevalence. Patients did not report discussing H. pylori or its cancer risk with providers. Discussion/Conclusion These data indicate the importance of considering SDoH in diagnosis and treatment of GC and its precursors, and educating providers and patients on H. pylori risks for GC.


| INTRODUCTION
Compared to non-Hispanic whites (NHWs), Latinos/ Hispanics have higher risk of developing multiple cancers, including gastric cancer (GC). 1 GC is the third-leading cause of cancer death worldwide 2 and was the sixth-and eighth-leading cause for Texas men and women, respectively, in 2012-2016. 3Mortality rates were twice as high for Latino/Hispanic than NHW men and 2.4 times higher for Latino/Hispanic than NHW women.GC incidence has been increasing in persons aged <50 years and Latino/ Hispanic women. 2,4In 2018, the probability of developing invasive GC at any age was twice as high in Latino/ Hispanic versus NHW men (1.6, or 1 in 64 vs. 0.8., 1 in 119), and three times higher in Latinas/Hispanics versus NHW women (1.2, 1 in 85 vs. 0.4, 1 in 227). 3Moreover, Latinos/ Hispanics are diagnosed at younger ages and more advanced stages compared to other ethnic groups, 3,5,6 which may contribute to higher mortality rates. 7Gastric adenocarcinomas (GCAs) account for approximately 90% of all GCs. 8 Latinos/Hispanics have higher GC rates in the distal stomach, 9 which has strong correlations with Helicobacter pylori (H.1][12] H. pylori infection accounts for 90% of GC cases, and is considered the primary GC risk factor (RF). 13 H. pylori influences several key elements in the Correa cascade of gastric carcinogenesis, including known GC precursors atrophic gastritis and intestinal metaplasia (IM). 14,15IM is highly prevalent in U.S. Latinos/Hispanics; its location, predominantly in the distal stomach is consistent with that of the majority of Latino/Hispanic GC cases. 16he American College of Gastroenterology treatment guidelines for H. pylori recommend bismuth-based quadruple therapy with clarithromycin, amoxicillin, and metronidazole. 17However, many practitioners still follow older guidance of triple therapy for H. pylori.This could be problematic in areas with high antibiotic resistance to clarithromycin and macrolides.
Latinos/Hispanics are disproportionately vulnerable to cancer due to the multiple social determinants of health (SDoH) including increased poverty, decreased education and low or no insurance. 3In South Texas (STX), a 38-county, majority Latino/Hispanic (nearly 70%) 18 region encompassing San Antonio south to the Lower Rio Grande Valley along the Texas-Mexico border, about 22% of residents on average had an income below 150% of the federal poverty line in 2018 (range 7.3%-35%), compared with the U.S. national average of 12%. 19For the period 2007-2010, an estimated 30% of STX residents were uninsured compared to 23% in the rest of Texas and 15% nationwide.Latinos had the highest uninsured rate (40%). 20DoH have contributed to racial-ethnic disparities in GC incidence.A study of the National Cancer Institute (NCI) Surveillance, Epidemiology and End Results (SEER) program from 2000 to 2014 found a 2.8-fold increased incidence of non-cardia GC in Latinos/Hispanics and blacks.Incidence increased with decreasing neighborhood socioeconomic status (nSES) for both ethnic groups. 21n this paper, we describe concurrent mixed-method research to investigate factors, including SDoH and their interactions, that contribute to disparities among Latinos/ Hispanics relative to non-Latinos, in diagnosis of H. pylori infection, GC, and known precursors.Findings draw upon secondary data collection/analysis of electronic health records (EHR) from two affiliated but independent health systems (quantitative); and semi-structured interviews of providers and a convenience sample of eligible patients in gastroenterology and oncology clinics on their experiences of facilitators of and barriers to care for these disorders (qualitative).

| MATERIALS AND METHODS
This study was approved by the Institutional Review Board of the University of Texas Health Science Center at San Antonio, 2019-387E and 2019-0534H.The study employed a concurrent mixed-methods approach to collect and analyze quantitative and qualitative data to better understand the full scope of access barriers leading to health disparities in GC preventive care.The quantitative data characterizes the level of disparities in access, while the qualitative data invites multilevel perspectives on causes of these differences.We collected data using both methods in parallel, and integrated and reported on them contiguously, that is, in separate sections of the Results before combining them in the Discussion. 22This will lay the groundwork for future studies and interventions aimed at improving GC preventive care.

| Study cohort variables
Variables of interest were extracted from structured data in the Clinical Research Informatics (CRI) data warehouse on all patients with gastric disorders (H.pylori infection, gastritis, gastric ulcer, atrophic gastritis, IM, and GCA, gastric lymphoma and gastric MALT lymphoma) diagnosed 2007-2020.Structured data was examined using regular expression of coding strings, for example, billing ICD9/10 diagnostic codes, key words, and Logical Observation Identifiers Names and Codes (LOINC). 23Median income and educational attainment was obtained from the 2016 American Community Survey 5-year Summary linked to patients based on their addresses; addresses were mapped to census block groups or zip codes and median income binned for the census group to de-identify it for researcher use.Zip code data was used to identify median income via the U.S. Census, 24 as well as estimates of geographical RF distribution.

| Quantitative analysis
Descriptive statistics were performed.Student's t-test was used to examine relationships between Latinos/Hispanics and NHWs for continuous variables, and chi-square test for categorical variables.Logistic regression models were used to examine differences between racial/ethnic groups with the outcomes of GC (vs.not) and other gastric diagnoses (atrophic gastritis, ulcer, gastritis, H.pylori, IM) controlling for demographics (age, gender) and socioeconomic covariates (patient-level payer status and the following geocoded variables: minority population, high school education, median income, unemployment, uninsured status, and poverty levels).The geocoded variables were transformed into quartiles to improve interpretation.Named gastric diagnoses were evaluated individually.The interactions between socioeconomic covariates and race/ ethnicities were tested to compare the effects of socioeconomic status within racial/ethnic strata.Time period was also adjusted for as a categorical covariate that represented 2-year intervals from 2007 to 2020.This approach provided estimation of odds ratios and 95% confidence intervals.All testing was two-sided at the significance level 0.05.

| Interview content and preparation
We developed semi-structured interview guides for both providers and patients based in the Practical, Robust Implementation and Sustainability Model (PRISM) to ensure interviews included questions to inform understanding of key needs, barriers and facilitators at organizational, provider, and patient levels (please see Figures S1 and S2 for full interview guides). 25The provider interview focused on: perceptions of H. pylori infection's impact on their patients' quality of life; perceived diagnosis rates of H. pylori and related gastric disorders; knowledge of and attitudes toward current practice guidelines 13 ; barriers to treatment initiation, completion and follow-up; and perceived effectiveness of testing, treatment and follow-up protocols.The patient interview focused on: understanding of the diagnosis and/or treatment plan; family history of H. pylori infection, gastric disorders and GC; barriers to treatment initiation, completion and follow-up; and satisfaction with received care.We targeted the patient interview to a 6th grade reading level, translated it into Spanish, and had it vetted by bilingual IHPR and UT Health faculty and staff experienced in qualitative research; interviews took 30-60 min to complete.Interviewers were bilingual and trained in interviewing techniques to most effectively elicit forthright responses.

| Recruitment: Providers
We contacted UHS and UTHealth providers in Primary Care, Gastroenterology and Oncology with an introductory email explaining the study and requesting participation.Additional contact methods (email or telephone follow-up) followed as needed to assess interest, answer questions, and schedule interviews; we asked all participants' permission to audio record interviews.We interviewed four oncologists, six gastroenterologists, and eight primary care physicians at both UHS and UTHealth.Responses were de-identified to protect confidentiality.The PI conducted all provider interviews.

| Recruitment: Patients
Eight oncology patients and seven gastroenterology patients were interviewed from convenience samples of patients scheduled to be seen at oncology clinics or for EGD procedures.Interviews were conducted on-site in-person or via telephone at the participant's convenience.Patients were compensated for their time.The PI and a bilingual individual with an MPH conducted all patient interviews.
All responses were de-identified to protect confidentiality; all interviews were audio recorded with participants' permission.All participants were provided with an information sheet explaining the purpose of the interview and the overall study.

| Qualitative data analysis
All interviews were recorded, transcribed, and analyzed for common themes using rapid qualitative approaches, specifically matrix techniques. 26,27We defined a preliminary set of analytic themes to capture barriers and facilitators to care and other relevant factors, consistent with PRISM.We created templates to summarize theme content and then further condensed them into matrices by theme and participant.These were reviewed and compared within and across participants by two independent research staff.Reporting of results was conducted according to consolidated criteria for reporting qualitative studies (COREQ). 28 The breakdown of diagnoses in our EHR-based sample was as follows: H pylori infection 36%; gastritis 19%; gastric ulcer 14%; chronic/atrophic gastritis 9.4%; IM 0.5%; GCA 2.3%; gastric MALT lymphoma 0.2%.Of all patients, 55% were tested for H. pylori, and of these 46% tested positive.

| Demographic characteristics and gastric cancer risk
Table 1 shows demographic characteristics and GC risk of the EHR-based sample (diagnoses 2007-2020).Over half of GC patients were Latino (Hispanic in Table 1) and male, and about a quarter had either Medicare or private insurance.Logistic regression adjusting for age and gender showed that Latinos had increased odds of GC diagnosis relative to whites (OR 1.24; 95% CI 1.02, 1.51; p = 0.031).Older age and male gender (p < 0.001; data not shown), and those with military insurance (insurance provided to military veterans) (OR = 2.67; CI 1.19, 5.40; p = 0.01) had increased odds of GC relative to younger age, female gender, and private insurance, respectively.Most year intervals were positively associated with GC (p < 0.001).In addition, low median income (4th quartile OR = 1.3; 95% CI 1.01, 1.69; p = 0.045) was also associated.

| Provider perspectives
Qualitative analyses of provider interviews revealed that providers were split on whether they viewed H. pylori prevalence as low or high in their patient population, but universally agreed they would treat it if diagnosed; however, only GIs and 2 PCPs reported preferring the recommended quadruple therapy.On being probed on guideline use, only this group identified the American Gastroenterology Association (AGA) guidelines as a key resource.All preferred the stool antigen test for diagnosis (consistent with guidelines) and cited symptoms (e.g., persistent epigastric pain, history of H. pylori infection with unclear eradication) as guides or "red flags" for the decision to test for H. pylori.Only site B providers, who serve low socioeconomic patients, and oncologists mentioned insurance and language as barriers to care, but six providers across specialties mentioned insurance policies as a needed improvement: specifically, they felt that patients could benefit from having more access to financial counselors, fewer requirement for prior authorization for drugs, and fewer changes to formularies, and expressed concerns some drugs in the AGA-recommended treatment cocktail were not covered.Providers were also split on whether they perceived the prevalence of antibiotic resistance as high or unknown; they cited varied perspectives on the source of resistance, from providers using incorrect regimens to problems with patient compliance, as well as system-level factors leading to patients not receiving the complete regimen.Four of six GI providers felt that referring providers were unaware or variably aware of H. pylori management guidelines.Nine primary care providers and GIs mentioned provider education as a needed improvement as well, particularly on AGA guidelines, appropriate H. pylori treatment regimens and eradication procedures, and when to refer to GI.

| DISCUSSION
In the context of increased risk for GC and precursor conditions among Latinos, we set out to examine relationships between SDoH and risk of GC and its precancerous conditions, including H. pylori infection, using a mixed-methods approach.We collected data using both methods in parallel, and integrated and reported on them contiguously, that is, in separate sections of the Results before combining them in the Discussion. 22First, we found that H. pylori diagnosis prevalence in this STX population was higher than national data (36% vs. 30%) 29 and that seroprevalence was approaching that of a study conducted among a Mexican-American population in Central Texas (46% vs. 57%). 30his also matches half of our interviewed providers' estimates of high H. pylori seroprevalence when testing levels are high (55% tested in this population, 46% H. pylori positive).However, a minority of providers preferred guidelinerecommended quadruple therapy for H. pylori, leading to a disconnect between testing and treatment practices.We also found that Latino/Hispanic ethnicity, older age and male gender, and military insurance were independently associated with increased risk of GC.When we studied interactions of ethnicity with SDoH, we found that lack of insurance and poverty increased minorities' risk for GC.These findings agree with a SEER 2000-2014 study that showed higher incidence rate ratios of non-cardia GC among minorities with decreasing nSES, 21 and a study that looked at nativity in Texas Latinos/Hispanics with GC. 31 Insurance is a common factor in these findings and was also mentioned as a barrier to care by some providers, who also mentioned a need for provider education.These data indicate an opportunity to educate providers on H. pylori prevalence and recommended treatment, and the need to improve insurance policies.Of note, several payer classes (non-Medicaid and non-Medicare), as well as people living in high-minority population communities, had lower odds of GC; the relationship between these findings and access to care issues should be investigated.
The importance of SDoH in cancer diagnosis and treatment has been shown in systematic reviews 32,33 and American Cancer Society Blueprint papers. 34Its importance in diagnosis and management of GC precursor disorders was further demonstrated by our findings that insurance and lack thereof; unemployment; poverty; lack of education; and living in a high-minority population neighborhood were associated with increased H. pylori infection risk.Combinations of these variables were also associated with other pre-GC disorders.
Although patients reported few overall barriers to care, the majority of patients interviewed did not discuss H. pylori with their provider, nor was its risk for GC discussed.Patients also indicated that they would encourage others to seek care sooner.As above, this indicates an opportunity and a need to educate providers and patients on H. pylori symptoms, risks, and treatment.
This study had several limitations.We did not examine H. pylori status as a factor for increased GC risk because the quality of the administrative data was variable.As the most well-established RF for non-cardia GC, this was assumed.In addition, as a potential mediator, H. pylori status was not adjusted for because it may suppress associations between RFs and outcomes.Nativity status was also not available; it has been shown to be an important SDoH for Hispanics/Latinos in Texas, related to lack of insurance and SES. 31 Although primary care providers were interviewed for this study, no patient interviews were conducted with patients in primary care settings due to COVID-19 limitations.Future studies including this population may point to early barriers to care that may be amenable to intervention.

| CONCLUSIONS
SDoH are important contributors to risk for GC and its precancerous precursors.They should be considered in future studies, especially interventions targeted at improving diagnosis and treatment of these disorders.Specifically, insurance policies should be improved so patients can more easily obtain treatment for H. pylori.Providers and patients would benefit from more education on H. pylori symptoms, risks and treatment.Including SDoH in diagnosis and treatment plans for minority patients can play an important role in mitigating the risk for GC and its precursors.

3. 1 . 3 |
Social determinants of health and gastric cancer risk

3.2 | Qualitative 3
.2.1 | Demographics Demographic breakdown of patients interviewed was as follows: median age 58 years; 50% female; 8 of 15 Latino/ Hispanic; majority white; 8 of 15 1st generation (i.e., immigrated from Mexico or other Latin American country); median time in U.S. if born in another country 15 years.
Sample characteristics, social determinants, and gastric cancer risk.
T A B L E 1 Race/ethnicity and SDoH interaction models.Abbreviations: BAORHIGHER_QUARTILE, Proportion with bachelors degree or higher; BELOWPOVERTY_QUARTILE, Proportion families below poverty; CI, confidence interval; MEDINCOME_QUARTILE, Median income quartile; MINORITYPOP_QUARTILE, Minority population quartile; NEARPOOR_ QUARTILE, Proportion near poverty: 100 and 125 percent of the poverty thresholds and referred to this group as near poor; NOHS_QUARTILE, Proportion without high school quartile; OR, odds ratio; POOR_QUARTILE, Proportion of population below poverty quartile; UNEMPLOYED_QUARTILE, Proportion unemployed quartile; UNINSURED_QUARTILE, Proportion uninsured quartile.
a Median (IQR); n (%).T A B L E 2 3.2.3|Patient perspectivesAbout half of patients reported variable or poor health (due to chemotherapy for oncology patients), but relatively few reported overall barriers to accessing care.A few patients mentioned delays in obtaining appointments, and the lack of enough providers and other clinic staff.Most oncology patients were on chemotherapy, while GI patients were on reflux medication.Most patients identified abdominal and throat symptoms as part of their gastric disorder and had undergone endoscopy for diagnosis.They also cited information sources on their disorder, including materials from their doctor and the internet.Patients varied in whether they recalled having any discussion of H pylori (HP) by setting of care.H. pylori was reported as not discussed with providers in seven of eight oncology patients compared to two of seven GI, and the majority received no information on its risk for cancer.Of those who discussed H. pylori, three mentioned the "stool test."All patients stated completing treatment was important; oncology patients cited survival while GI patients focused on symptom control.However, 7 of 15 cited side effects as a barrier.All patients were satisfied with their care overall.A few patients and providers both pointed to the need for additional clinic staff.When asked what advice they would give family members in a similar situation, six patients indicated they would advise their families to consult a doctor sooner for symptoms.